Colony stimulating factors (CSF) are a group of specific regulatory glycoproteins that stimulate hematopoietic cell proliferation and differentiation. They are also believed to affect the activity of subpopulations of mature hematopoietic cells which are important in a host defense against infection.
The study of hematopoiesis and the potential role of the hematopoietic cells in the immune response requires the ability to maintain and grow hematopoietic progenitor cells in vitro and in vivo. Thus CSFs may be employed as reagents for clinical testing and research study of the cells of the hematopoietic and possibly the immune systems. Several CSFs have been identified which may be useful for these purposes, e.g., CSFs that control granulocyte and macrophage populations, and CSFs that stimulate mast cells and stem cells. Several human granulocyte and/or macrophage CSFs have presently been identified [See D. Metcalf, "The Molecular Biology and Functions of the Granulocyte-Macrophage Colony Stimulating Factors," Blood, 67 (2): 257-267 (1986).]
A cDNA sequence for human urinary CSF-1 has been reported by E. S. Kawasaki, et al., Science, 230: 291-196 (1985), which when expressed in a COS cell transient expression system, produced a protein that competed with labeled murine CSF-1 in a radio-receptor assay. The protein also reportedly stimulated mouse bone marrow proliferation, resulting in predominantly monocytic lineage type colonies in the mouse bone marrow assay. The protein's biological activity was inhibited by neutralizing antisera for CSF-1.
These CSF glycoproteins have therapeutic potential in the treatment of diseases characterized by a decreased level of production of hematopoietic cells. In addition they may prove useful as activators of mature white cells in cases of serious infection. Leukopenia, a reduction in the number of circulating leucocytes (white cells) in the peripheral blood is a common affliction that may be induced by exposure to radiation or chemical carcinogens and exposure to certain viruses. It is often a side effect of various forms of cancer therapy. Therapeutic treatment of leukopenia with presently available drugs is ineffective and can result in undesirable side effects. There remains a need in the field for effective therapeutic agents for naturally occurring or radiation-induced leukopenia.
The ability to make large quantities of a protein exhibiting a high degree of human CSF activity will facilitate the study of the biological properties of the progenitor cells involved in the formation of all types of circulating blood cells. The availability of such proteins will also aid in evaluating the roles of other growth factors as well as provide potential therapeutic agents for treating leukopenias, generalized cytopenias and serious infections and potentially aid in regulating immune functions.